1. Technical Field
The invention relates to the estimation of the apparent age of in vivo skin tissue. More particularly, the invention relates to the instrumentation and method by which the age and general tissue parameters of subjects can be estimated and classified through noninvasive tissue measurements.
2. Description of the Prior Art
Near-infrared (NIR) tissue spectroscopy is a promising noninvasive technology that bases measurements on the irradiation of a tissue site with NIR energy in the 700-2500 nanometer wavelength range. The energy is focused onto an area of the skin and propagates according to the scattering and absorption properties of the skin tissue. Thus, the reflected or transmitted energy that escapes and is detected provides information about the tissue volume encountered. Specifically, the attenuation of the light energy at each wavelength is a function of the structural properties and chemical composition of the tissue. Tissue layers, each containing a unique heterogeneous particulate distribution, affect light absorbance through scattering. Chemical components such as water, protein, fat and blood analytes absorb light proportionally to their concentration through unique absorption profiles or signatures. The measurement of tissue properties, characteristics or composition is based on detecting the magnitude of light attenuation resulting from its respective scattering and/or absorption properties. The chronological age and type and duration of environmental exposure of skin tissue have a pronounced effect on the properties of tissue and is a primary factor in tissue variability between individuals. See, for example, W. Andrew, R. Behnke, T. Sato. Changes with advancing age in, the cell population of human dermis, Gerontologia, vol. 10, pp. 1-19, (1964/65); W. Montagna, and K. Carlisle. Structural changes in ageing human skin, The Journal of Investigative Dermatology, vol. 73, pp. 47-53, 1979. J. Brocklehurst, Textbook of Geriatric Medicine and Gerontology, Churchill Livingstone, Edinburgh and London, pp.593-623 (1973).
Therefore, NIR tissue spectroscopy can be used to detect, quantify, and monitor age related effects in tissue through a noninvasive measurement process. Moreover, NIR tissue spectroscopy has particular benefit in several areas including estimation of blood analytes, assessment and monitoring of therapies. used to reduce the effects of ageing in tissue and diagnosis and quantification of tissue damage.
Blood Analyte Prediction
While noninvasive prediction of blood analytes, such as blood glucose concentration, has been pursued through NIR spectroscopy, the reported success and product viability has been limited by the lack of a system for compensating for structural variations between individuals that produce dramatic changes in the optical properties of the tissue sample See, for example, O. Khalil. Spectroscopic and clinical aspects of non-invasive glucose measurements, Clin Chem (1999) vol. 45, pp.165-77, and J. Roe and B. Smoller, Bloodless Glucose Measurements, Critical Reviews in Therapeutic Drug Carrier Systems, vol. 15, no. 3, pp. 199-241 (1998).
These differences are largely anatomical and provide distinct systematic spectral absorbance features or patterns that can be related directly to specific characteristics such as dermal thickness, protein levels, structure of collagen bundles, dermal thinning, hydration, flattening of the epidermal-dermal junction and thickness of the subcutaneous layer. While the absorbance features are repeatable by subject over short periods of time, over a population of subjects they produce confounding nonlinear spectral variation. In addition, the changes of skin tissue of an individual as the result of chronological ageing and/or environmental exposure lead to profound differences in the volume of tissue sampled by the NIR measurement device. Therefore, differences between subjects and within subjects over time are a significant obstacle to the noninvasive measurement of blood analytes through NIR spectral absorbance.
Previously, in the parent application to the current application, S. Malin and T. Ruchti, An Intelligent System For Noninvasive Blood Analyte Prediction. U.S. patent application Ser. No. 09/359,191, filed Jul. 22, 1999 an apparatus and procedure for substantially reducing this problem by classifying subjects according to major skin tissue characteristics prior to blood analyte prediction was disclosed. The selected characteristics are representative of the properties of the actual tissue volume irradiated and the amount of the target analyte that is sampled. By grouping individuals according to the similarity of spectral characteristics representing the tissue structure, the nonlinear variation described above is reduced and estimation of blood analytes becomes more accurate. Specifically, classification of NIR spectral data according to the apparent age or condition of the tissue will improve the accuracy and robustness of models for estimating tissue/blood parameters, such as blood analytes, through the significant reduction of sample variability without the addition of other measurement devices (see S. Malin and T. Ruchti, An Intelligent System For Noninvasive Blood Analyte Prediction, U.S. patent application Ser. No. 09/359,191, filed Jul. 22, 1999).
Apparent Ageing of Skin Tissue
The effects of ageing on skin tissue include two separate phenomena: chronological and photo ageing. Chronological ageing is typified by natural changes in the skin over time, such as dermal thinning, changes in level of hydration, flattening of the epidermal-dermal junction and reduced sebum/sweat production.
For example, see A. Oikarinen, Ageing of the skin connective tissue: how to measure the biochemical. and mechanical properties. of ageing dermis, Photodermatology Photoimmunology and Photomedicine (1994) vol. 10, pp. 47-52; N. Fenske, and C. Lober, Structural and functional changes of normal ageing skin, J Am Acad Dermatol (1996) vol. 15, pp. 571-583; M. Gniadecka, and G. Jemec, Quantitative evaluation of chronological ageing and photo ageing in vivo: studies on skin echogenicity and thickness, Br J Dermatol (1998) vol. 139, pp. 815-821.
Photo ageing is an alteration or damaging of skin as a result of sun exposure, manifested by dryness, solar elastosis, irregular pigmentation and fine wrinkling, and is the cause of premature ageing of skin. See, for example R. Stern, The Measure of Youth, Arch Dermatol (1992) vol. 128, pp. 390-393.
Ultrasound has been used to reveal that changes in the upper dermis are related to photo ageing and changes in the lower dermis are related to chronological ageing. See A. Oikarinen, Ageing of the skin connective tissue: how to measure the biochemical and mechanical properties of ageing dermis, Photodermatology Photoimmunology and Photomedicine (1994) vol. 10, pp. 47-52. The upper dermis becomes thicker (solar elastosis) with increased sun exposure and the lower dermis degrades with chronological age. See J. Rigal, C. Escoffier, B. Querleux, B. Faivre, P. Agache, J. Leveque, Assessment of Ageing of the Human Skin by In Vivo Ultrasonic Imaging, Society for Investigative Dermatology (1989) vol. 93, pp. 621-625.
As a result of societal pressure for tanned young skin, pharmaceutical and cosmetic companies have been developing and marketing products that claim to repair the effects of photo-damage to skin and restore skin to its youthful condition. The ability to quantitatively measure the apparent age or condition of tissue is useful in determining the effectiveness of topical drugs used to reverse damage due to photo ageing . See R. Stern, The Measure of Youth, Arch Dermatol, (1992), vol. 128, pp. 390-393. An in vivo, quantitative technique would be of great benefit in assessing the effectiveness of treatments for photo-damaged tissue. See M. Quan, C. Edwards, and R. Marks, Non-invasive In Vivo Techniques to Differentiate Photodamage and Ageing in Hu7man Skin, Acta Derm Venereol, vol. 77, pp. 416-419 (1997).
However, no technique has been reported for quantitatively determining apparent age on the basis of a noninvasive measurement. Existing methods for age determination generally rely on invasive procedures or subjective evaluation. The amount of photo-damage and the effects of age-reversing drugs are typically determined by visual inspection of the skin by a trained individual and subsequent assignment of a grade representing the degree of damage. Several groups have proposed methods using standardized photographs representation the different degrees of sun damage in an attempt to standardize the age ratings. These methods have been found to be subjective and not repeatable. Furthermore, these qualitative methods only provide a surface measurement of the effectiveness of the product being tested and do not provide any information. about true structural or chemical changes in the tissue. See R. Stern, The measure of Youth, Arch Dermatol, vol. 128, pp. 390-393 (1992).
The present invention provides a method and apparatus for non-invasively determining the apparent age tissue, in vivo. A spectroscopic apparatus in conjunction with an optical interface is used to measure tissue properties and characteristics that are manifested spectrally and that vary systematically according to the subject""s age and environmental exposure. A novel method is disclosed that uses in vivo, non-invasive NIR measurements to estimate the apparent age of the skin and/or classify the skin according to predefined age group categories.
The procedure for age estimation employs a calibration model that is empirically derived from a set of exemplary samples consisting of NIR tissue measurements and the actual chronological age of a population of subjects. The model is a set of parameters and computer generated code that is implemented to estimate the subject""s age. The estimation consists of an actual age determination in years and one or more relative property magnitudes that reveal information regarding the tissue properties of the sampled tissue volume.
The apparent age estimate provides a reliable and repeatable quantitative measure of the condition of the skin with respect to the combined effects of chronological ageing and photo ageing. In addition, magnitude of the two types of ageing is deduced from NIR measurements by targeting specific tissue volumes and/or decomposing the measurements through multivariate factor analysis to reveal underlying variation correlated to specific ageing related tissue parameters such as dermal thickness and hydration. The resulting age estimation and/or classification is also suitable for categorization of spectral data prior to blood analyte prediction.